A Managed Care Organization's Initiative to Improve Patient Safety in the Use of Concentrated Insulin

■■ A Managed Care Organization’s Initiative to Improve Patient Safety in the Use of Concentrated Insulin As obesity becomes more prevalent, so have cases of newly diagnosed diabetes. According to 2008 estimates, more than 18 million American adults have diabetes and 12.4% of them take both insulin and oral medications to treat their disease. Patients on both insulin and oral medications commonly present a therapeutic challenge to clinicians attempting to attain tight glycemic control and hemoglobin A1c levels within a desirable range. Often, this group will develop insulin resistance, defined by Cochran et al. as a situation where a patient requires greater than 200 units of insulin daily. Because of this problem, an increase has occurred in the utilization of concentrated U-500 regular insulin. In 1952, U-500 insulin was introduced to market in the United States as beef regular insulin. Later on, the pork version was approved in 1980, followed by the human version in 1997. From June 2007 to June 2009, utilization rates of human U-500 insulin jumped by 137%, mostly because of increases in the number of obese, clinically insulin-resistant patients with type 2 diabetes. Understanding of the pharmacokinetics and pharmacodynamics of U-500 insulin is increasing along with its use. Cochran et al. described that U-500 has a pharmacokinetic profile similar to that of U-100 neutral protamine Hagedorn (NPH) insulin, with slowed absorption and longer duration than U-100 regular insulin. In addition, although an inverse relationship generally exists between insulin concentration and absorption, the absorption curves for U-500 appear to differ in obese versus nonobese patients and with lower, subtherapeutic doses versus higher, clinically therapeutic doses.


■■ A Managed Care Organization's Initiative to Improve Patient Safety in the Use of Concentrated Insulin
As obesity becomes more prevalent, so have cases of newly diagnosed diabetes. According to 2008 estimates, more than 18 million American adults have diabetes and 12.4% of them take both insulin and oral medications to treat their disease. 1,2 Patients on both insulin and oral medications commonly present a therapeutic challenge to clinicians attempting to attain tight glycemic control and hemoglobin A1c levels within a desirable range. Often, this group will develop insulin resistance, defined by Cochran et al. as a situation where a patient requires greater than 200 units of insulin daily. 3 Because of this problem, an increase has occurred in the utilization of concentrated U-500 regular insulin.
In 1952, U-500 insulin was introduced to market in the United States as beef regular insulin. Later on, the pork version was approved in 1980, followed by the human version in 1997. From June 2007 to June 2009, utilization rates of human U-500 insulin jumped by 137%, mostly because of increases in the number of obese, clinically insulin-resistant patients with type 2 diabetes. 4 Understanding of the pharmacokinetics and pharmacodynamics of U-500 insulin is increasing along with its use. Cochran et al. described that U-500 has a pharmacokinetic profile similar to that of U-100 neutral protamine Hagedorn (NPH) insulin, with slowed absorption and longer duration than U-100 regular insulin. 3 In addition, although an inverse relationship generally exists between insulin concentration and absorption, the absorption curves for U-500 appear to differ in obese versus nonobese patients and with lower, subtherapeutic doses versus higher, clinically therapeutic doses. 4

U-500 Insulin Is a High-Alert Medication
Because of its high concentration, U-500 insulin is generally regarded as a high-alert drug. The Institute for Safe Medication Practices (ISMP) has repeatedly reported the need for caution and the potential for medication errors when using U-500. For example, in 2001 they recommended that only tuberculin syringes-not U-100 syringes-be used to measure U-500 insulin to ensure correct dosing. 5 To illustrate the problem with U-100 syringes, the ISMP safety alert described a case in which an endocrinologist wrote an order for "25 unwits of U-500 insulin" to be given in the morning. The intended insulin dose was 125 units, but because the physician did not specify the "25 unit" marking to be used on the U-100 insulin syringe scale, the patient only received one-fifth of the prescribed dose, or 25 units. 5 In 2008, the manufacturer of U-500 insulin conducted a comprehensive evaluation of its database to search for potential errors associated with the medication. The evaluation came in response to a report released a few months earlier by the U.S. Food and Drug Administration (FDA) Adverse Event Reporting

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System. The manufacturer identified 22 cases of medication errors in its database, with 82% of them related to administration or dispensing. 4 Because reporting of medication errors to the manufacturer is voluntary, the actual numbers may be higher.
In the outpatient setting, U-100 insulin syringes are commonly used for the administration of U-500 insulin. A patient is trained to measure his or her "dose" by drawing up to a certain marking on the U-100 syringe. However, problems can arise with this approach. If a patient is hospitalized, he or she may incorrectly report the U-100 marking as his or her actual dose of insulin. In addition, when physicians order concentrated insulin in this manner, the dose is ambiguous, and the dispensing pharmacist may counsel a patient incorrectly, sometimes contradicting what the office staff previously said to the patient.

Intervention to Increase Access to Tuberculin Syringes
Thorough patient education on the use of U-500 insulin can help decrease these medication errors. The prescriber can also help by ordering the actual insulin dose with the volume. Another strategy is to avoid use of U-100 syringes and use only tuberculin syringes with U-500 insulin.
In keeping with this recommendation from the ISMP to use tuberculin syringes rather than U-100 syringes, EmblemHealth, a health plan with about 3.3 million members, undertook an initiative to increase safety with the use of U-500 insulin by improving access to tuberculin syringes. Recognizing that clinicians tend to favor U-100 syringes because of their greater availability and lower cost, EmblemHealth created a policy in which tuberculin syringes are covered under the pharmacy benefit, effective November 1, 2010. Whenever a claim for U-500 insulin is processed, the online claims adjudication process system automatically allows coverage of the tuberculin syringes at the point of service. The tuberculin syringe claims will adjudicate under either the first-or second-tier copayment of the member, depending on the pharmacy benefit rider for that member.
To increase recognition of this new policy, EmblemHealth mailed letters to all plan physicians or nurse practitioners who were identified in pharmacy claims as the prescribers of U-500 insulin for dates of service from April 1, 2010, through September, 30, 2010. The letters were also sent to all endocrinologists (n = 1,013) in EmblemHealth's physician database system. In addition, information about the new policy was posted on EmblemHealth's website. 6 A total of 1,037 letters were mailed in October 2010. The letter described the new policy, how to properly prescribe concentrated insulin (i.e., actual U-500 insulin dose with the corresponding volume of the dose), and why ISMP recommends the use of tuberculin syringes with U-500 insulin.
A review of our paid pharmacy claims database revealed